P1186: RETROSPECTIVE STUDY: ZANUBRUTINIB COMBINED WITH R-CHOP OR R-CHOP REGIMEN IN THE TREATMENT OF UNTREATED NON-GERMINAL CENTER B-CELL SUBTYPE DIFFUSE LARGE B-CELL LYMPHOMA WITH EXTRANODAL INVOLVEMENT.
Authors: LI Caixia, Hongzhi Geng, Xiangping Zong, Ying Zhang, Sixun Jia, LI Jiaqi, Jin Zhou, Depei Wu
Journal: HemaSphere (2023)

Topic: 19. Aggressive Non-Hodgkin lymphoma - Clinical Background: Patients with multiple extranodal involvement and non-GCB subtype DLBCL have poor response rate to R-CHOP treatment, our clinical trail (number NCT 04835870) for patient with non-GCB DLBCL with extranodal involvement has observed satisfactory results, we retrospectively analyzed the treatment outcomes of these patients receiving ZR-CHOP regimen and standard treatment during the same period. Aims: Retrospective statistical analysis of the treatment effect of patients receiving ZRCHOP treatment and standard treatment Methods: We retrospectively analyzed that from Oct. 2020 to Apr. 2022, all DLBCL patients with extranodal involvement who received ZR-CHOP treatment and standard treatment, patients with GCB subtype and patients with disease stage I were not included in the analysis. Primary endpoints is PFS based on Lugano (2014) Criteria. Secondary endpoints included overall response rate (ORR), complete response (CR) and duration of response (DOR) based on Lugano (2014) Criteria, safety and tolerability, and explore whether the oncogenic mutation detected by next-generation sequencing (NGS) have any difference in treatment efficacy. Results: 23 patients received ZR-CHOP regime with a median follow-up of 16.7 months (7.7~28.2months), compared with 47 patients received R-CHOP with a median follow-up of 17.2 months(7.9~27.9months) in the same period, there is no significant difference in the clinical characteristics between the two groups through statistical analysis. The primary endpoint was not reached. The ORR of patients received ZR-CHOP and R-CHOP were 91.3%(n=21) and 68.1%(n=32), of which 82.6%(n=19) and 61.7%(n=29) were CR, 8.7%(n=2) and 6.4%(n=3) were partial response (PR), 8.7%(n=2) and 25.5%(n=15) was progression disease (PD) or stable disease. The ORR was statistically significant in all patients(P=0.04). At present, there is no significant difference in OS between the two groups(91.3% vs 83.0%, P=0.44), which may be that the follow-up time is not long enough, the PFS of the two groups was statistically significant(82.5% vs 53.2%, P=0.02) and in addition, PFS of patients younger than 60 years old(90% vs 50%, P=0.04), patients with ≥ 2 extrandol involvement(78.6% vs 28.6%, P=0.01), patients with III/IV disease stage(77.8% vs 45.9%, P=0.04), and patients with double expression lymphoma(87.5% vs 25%, P=0.02) was significantly superior than that of standard treatment. No significant increase was observed in adverse events caused by oral zanubrutinib. The ≥3 grades hematological adverse events during the treatment were neutropenia (56.5% and 46.8%), thrombocytopenia (26.1% and 6.4%) and anemia (8.7% and 8.5%), and the main grade ≥3 non hematological toxicity was pulmonary infection (21.7% and 19.1%). Atrial fibrillation was observed in two (8.7%) patients with oral Zanubrutinib, but none of them affected the follow-up treatment. No patient had fatal adverse events. NGS was assessed in 19 of 23 patients. Oncogenic mutations closely related to DLBCL pathogenesis were assessed in 19 of 23 patients, genotyping of patients can be divided into 4 MCD, 3 BN2, 3 ST2,1 MCD/ BN2 genetically composite and 8 cases of Others. B-cell receptor and NF-κB pathway gene mutations were detected in 10 patients occurred in MYD88 (7 of 19, including 5 with MYD88L265P), CD79B (4 of 19), CARD11 (5 of 19), TNFAIP3 (2 of 19). 8 of 10 them sustain response.Summary/Conclusion: Our results showed that ZR-CHOP may be a safe and better scheme for non-GCB DLBCL patients with extranodal involvement. Compared with standard first-line treatment, patients in specific subgroups may obtain better efficacy Keywords: Extranodal lymphoma